Insufficient Evidence
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2021 ◽  
pp. bjophthalmol-2021-318892
Ankit Singh Tomar ◽  
Paul T Finger ◽  
Brenda Gallie ◽  
Tero Kivelä ◽  
Ashwin Mallipatna ◽  

AimTo investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding.MethodsMulticentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method.ResultsClinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06).ConclusionThis international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

2021 ◽  
Katharina Doni ◽  
Stefanie Bühn ◽  
Alina Weise ◽  
Nina-Kristin Mann ◽  
Simone Hess ◽  

Abstract BackgroundWe aim to assess the safety of dipeptidylpeptidase-4 inhibitors (DPP4s) in older type 2 diabetes patients with inadequate glycaemic control. MethodsWe included RCTs in older (≥65 years) patients with type 2 diabetes. The intervention group was treated with any DPP4. A systematic search in MEDLINE and EMBASE was performed in December 2020. For assessing risk of bias, the RoB 2 tool was applied. The quality of evidence was assessed using GRADE. We pooled outcomes using random-effects meta-analyses. ResultsWe identified 16 RCTs that included 19,317 patients with a mean age >70 years. The mean HbA1c ranged between 7.1g/dl and 10.0g/dl.Adding DPP4s to standard alone care may increase mortality slightly (RR 1.04; 0.89-1.21). Adding DPP4s to standard care increases the risk for hypoglycaemia (RR 1.08; 95%CI 1.01-1.16), but difference in overall adverse events is negligible.DPP4s added to standard care likely reduce mortality compared to sulfonylureas (RR 0.88; 0.75-1.04). DPP4s probably reduce the risk for hypoglycaemia compared to sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible.There is insufficient evidence on hospitalizations, falls, fractures, renal impairment, and pancreatitis. Conclusion There is no evidence that DPP4s in addition to standard care decrease mortality but DPP4s increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously because even in drugs with a good safety profile like DPP4s. In the case second-line treatment is necessary, DPP4s appear to be superior to sulfonylureas. RegistrationPROSPERO: CRD42020210645

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2612
Gaku Yamanaka ◽  
Shinji Suzuki ◽  
Natsumi Morishita ◽  
Mika Takeshita ◽  
Kanako Kanou ◽  

Riboflavin, a water-soluble member of the B-vitamin family, plays a vital role in producing energy in mitochondria and reducing inflammation and oxidative stress. Migraine pathogenesis includes neuroinflammation, oxidative stress, and mitochondrial dysfunction. Therefore, riboflavin is increasingly being recognized for its preventive effects on migraines. However, there is no concrete evidence supporting its use because the link between riboflavin and migraines and the underlying mechanisms remains obscure. This review explored the current experimental and clinical evidence of conditions involved in migraine pathogenesis and discussed the role of riboflavin in inhibiting these conditions. Experimental research has demonstrated elevated levels of various oxidative stress markers and pro-inflammatory cytokines in migraines, and riboflavin’s role in reducing these marker levels. Furthermore, clinical research in migraineurs showed increased marker levels and observed riboflavin’s effectiveness in reducing migraines. These findings suggest that inflammation and oxidative stress are associated with migraine pathogenesis, and riboflavin may have neuroprotective effects through its clinically useful anti-inflammatory and anti-oxidative stress properties. Riboflavin’s safety and efficacy suggests its usefulness in migraine prophylaxis; however, insufficient evidence necessitates further study.

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Nathan T. Lee ◽  
Fatimah Ahmedy ◽  
Natiara Mohamad Hashim ◽  
Khin Nyein Yin ◽  
Kai Ling Chin

Stroke is one of the most deliberating causes of mortality and disability worldwide. Studies have implicated Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene as a genetic factor influencing stroke recovery. Still, the role of BDNF polymorphism in poststroke aphasia is relatively unclear. This review assesses the recent evidence on the association between the BDNF polymorphism and aphasia recovery in poststroke patients. The article highlights BNDF polymorphism characteristics, speech and language interventions delivered, and the influence of BNDF polymorphism on poststroke aphasia recovery. We conducted a literature search through PubMed and Google Scholar with the following terms: “brain derived-neurotrophic factor” and “aphasia” for original articles from January 2000 until June 2020. Out of 69 search results, a detailed selection process produced a total of 3 articles that met the eligibility criteria. All three studies included Val66Met polymorphism as the studied human BDNF gene. One of the studies demonstrated insufficient evidence to conclude that BDNF polymorphism plays a role in poststroke aphasia recovery. The remaining two studies have shown that Met allele genotype (either single or double nucleotides) was associated with poor aphasia recovery, in either acute or chronic stroke. Carriers of the Val66Met polymorphism of BDNF gave a poorer response to aphasia intervention and presented with more severe aphasia.

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Kiran Mehta ◽  
Renuka Sharma ◽  
Vishal Vyas ◽  
Jogeshwarpree Singh Kuckreja

Purpose The existing literature on venture capitalists’ (VCs’) exits provides insufficient evidence regarding factors affecting the exit decision. This study aims to identify these factors and examine how VC firms do ranking or prioritize these factors. Design/methodology/approach The study is based on primary data. The qualitative analysis was done to develop the survey instrument. Fuzzy analytical hierarchical process, which is a popular method of multi-criteria decision modeling, is used to identify or rank the determinants of exit strategy by venture capital firms in India. Findings Broadly, eight determinants of exit strategy are ranked by VCs. A total of 33 statements describe these eight determinants. The results are analyzed on the basis of four measures of VCs’ profile, i.e. age of VC firm, number of start-ups in portfolios, type of investment and amount of investment. Research limitations/implications The survey instrument needs to be validated with a larger sample size and other financial backers than VCs. Practical implications The study has direct managerial implication for VC firms as it provides useful information regarding the determinants of exit strategy by VC firms in India. These findings can provide necessary information to other financial backers too, viz., angel investors, banks, non-banking financial institutions and other individual and syndicated set-ups providing funding to start-ups. Originality/value The current research is unique as no prior study has explored the determinants of VCs exit strategy and prioritizing these determinants.

Zygote ◽  
2021 ◽  
pp. 1-4
Qin Wang ◽  
Ashley Ulker ◽  
Hongfeng Wang ◽  
Bin Wu ◽  
Aijun Yang ◽  

Summary The finding of conjoined oocytes is a rare occurrence that accounts for only 0.3% of all human retrieved oocytes. This phenomenon is quite different from that of a traditional single oocyte emanating from one follicle, and may result in dizygotic twins and mosaicism. Given the insufficient evidence on how to approach conjoined oocytes, their fate is variable among different in vitro fertilization (IVF) centres. In this observational report, we propose a new protocol for the use of these conjoined oocytes using intracytoplasmic sperm injection (ICSI), laser-cutting technique and next-generation sequencing (NGS). The first case report demonstrates that conjoined oocytes can penetrate their shared zona pellucida (ZP) at Day 6. The second case is that of a 25-year-old female patient who underwent a successful embryo transfer cycle after removal of one oocyte in which a pair of conjoined human oocytes underwent ICSI, laser-cutting separation and NGS testing. The patient achieved pregnancy and gave birth to single healthy female originally derived from conjoined oocytes. This case provided a means through which normal pregnancy may be achieved from conjoined oocytes using laser-cutting separation techniques. The protocol described may be especially beneficial to patients with a limited number of oocytes.

2021 ◽  
pp. 153944922110292
Jodie Schroder ◽  
Lynette Mackenzie

Increased cancer survivorship means more people are living with cancer-related fatigue (CRF), which is associated with activity performance limitations, restricted participation in meaningful life roles, and reduced quality of life. To identify whether non-pharmacological interventions that are effective in minimizing CRF also have an impact on everyday activity performance and participation outcomes for adult cancer survivors. This is a systematic review with narrative synthesis. Eight databases were searched (Medline, CINAHL, PsychINFO, EMBASE, Scopus, OT Seeker, CENTRAL, Cochrane SR database), from 2000 to 2020 for randomized controlled trials of effective non-pharmacological CRF interventions in adult cancer survivors with fatigue. A total of 5,762 studies were identified of which 29 studies were reviewed. In 28 studies, quality of life was investigated as a primary or secondary outcome, where concepts of participation or activity performance were used. Review findings indicate there is insufficient evidence to determine whether activity performance and participation is affected by CRF interventions.

2021 ◽  
Vol 11 (1) ◽  
Sanae Hosomi ◽  
Tetsuhisa Kitamura ◽  
Tomotaka Sobue ◽  
Hiroshi Ogura ◽  
Takeshi Shimazu

AbstractSurgeons and medical staff attend academic meetings several times a year. However, there is insufficient evidence on the influence of the “meeting effect” on traumatic brain injury (TBI) treatments and outcomes. Using the Japan Trauma Data Bank, we analyzed the data of TBI patients admitted to the hospital from 2004 to 2018 during the national academic meeting days of the Japanese Association for Acute Medicine, the Japanese Society of Intensive Care Medicine, the Japanese Association for the surgery of trauma, the Japan Society of Neurotraumatology and the Japan Neurosurgical Society. The data of these patients were compared with those of TBI patients admitted 1 week before and after the meetings. The primary outcome was in-hospital death. We included 7320 patients in our analyses, with 5139 and 2181 patients admitted during the non-meeting and meeting days, respectively; their in-hospital mortality rates were 15.7% and 14.5%, respectively. No significant differences in in-hospital mortality were found (adjusted odds ratio, 0.93; 95% confidence interval, 0.78–1.11). In addition, there were no significant differences in in-hospital mortality during the meeting and non-meeting days by the type of national meeting. In Japan, it is acceptable for medical professionals involved in TBI treatments to attend national academic meetings without impacting the outcomes of TBI patients.

Aline Pereira da Rocha ◽  
Alvaro Nagib Atallah ◽  
José Mendes Aldrighi ◽  
Andréa Larissa Ribeiro Pires ◽  
Maria Eduarda dos Santos Puga ◽  

2021 ◽  
pp. 60-78
Desmond E. Ighravwe ◽  
Sunday A. Oke

The management of waste with the limited workforce and trucks is a complicated problem. Currently, there is insufficient evidence in literature on how this process could be optimised. In this article, two new models on genetic algorithm and differential evolution were developed to jointly optimise the cost and human reliability of a municipal solid waste (MSW). It optimised this system’s benefit-cost and established the relationship between a MSW’s workforce and truck allocation. Although prior research has revealed relationships among cost, workforce strength, and truck allocation activities, however, the nature of this relationship and the unique attribute of workers’ reliability to influence the total operating cost and the benefit-cost ratio have not been thoroughly understood. A case study of a MSW agency in Nigeria was used to demonstrate the applicability of the proposed model. The results obtained showed preference to the differential evolution algorithm’s results. This article contributes to MSW in the following ways: it presents a model to assign reliability to workforce in a MSW system based on evolutionary algorithms performance, and it optimises a MSW system’s total operating cost and the benefit-cost ratio concurrently.

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